Sodium Carbonate → HCID 70663425, compound

HRID 878366Notes

Reaction equation

HRID 878366 reaction equation
FC1C=CC=C(OC)C=1[C:10]1[CH:15]=[CH:14][N:13]=[CH:12][C:11]=1[N:16](CC(F)(F)F)C(=O)C1C=C(C(F)(F)F)C=C(S(C)(=O)=O)C=1.[F:38][C:39]([F:51])([F:50])[O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1B(O)O.[C:52]([O-:55])([O-])=[O:53].[Na+].[Na+].C1(P([C:71]2[CH:76]=[CH:75]C=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:77]([O-])(O)=O.[Na+]>COCCOC.CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O>[C:76]([O:55][C:52](=[O:53])[NH:16][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][C:10]=1[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=1[O:40][C:39]([F:51])([F:50])[F:38])([CH3:75])([CH3:71])[CH3:77]

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 86670807N-[4-(2-Fluoro-6-methoxy-phenyl)-pyridin-3-yl]-3-methanesulfonyl-N-(2,2,2-trifluoro-ethyl)-5-trifluoromethyl-benzamide2×

Product 1

HCID 70663425HCID 70663425, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester (500 mg, 1.56 mmol, example 85, intermediate d) in 6 mL DME were added 2-trifluoromethoxyphenylboronic acid (643 mg, 3.12 mmol) and 2M aqueous Na2CO3 solution (2.0 mL) and the reaction mixture was purged with nitrogen for 15 min. Then Pd(OAc)2 (36 mg, 0.16 mmol) and triphenylphosphine (82 mg, 0.31 mmol) were added and the reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL EtOAc and the layers were separated. The aqueous layer was extracted with 30 mL EtOAc. The combined organic layer was washed with 30 mL brine, dried over Na2SO4 and evaporated. The residue was purified by column chromatography eluting with a gradient of n-hexane:EtOAc (80:20 to 70:30) to yield the desired compound as a light yellow sticky liquid (440 mg, 80%). LC-MS: m/z=355.0 [M+H]+.

Workup

  1. customthe reaction mixture was purged with nitrogen for 15 min
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with 30 mL EtOAc
  4. washThe combined organic layer was washed with 30 mL brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by column chromatography
  8. washeluting with a gradient of n-hexane:EtOAc (80:20 to 70:30)

Sources & evidence

ORD record
ord-559a90fdbdec45d8a0a789f84311c84a
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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